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THYROID HORMONES IN SERIOUS NON-THYROIDAL ILLNESS
1070 Births
Survey 1975’ shows that 68.8% of all mothers received pethidine or levallorphan, a substantial increase from the position in 1958.6 Not only are more mothers receiving this narcotic but dose levels seem to be rising. One textbook,’ for example, suggests that "the usual dose is 150 to 200 mg by intramuscular injection, which may be repeated in 2 hours. A total dose of 300-400 mg is commonly employed though in some hospitals much larger doses are given." Those familiar with the evidence of the physiological and psychological effects 10
of this drug on mothers* and babies9 may well conclude that abuse is very widespread and growing. The evidence for the safety of epidurals is not much more reassuring. Forceps deliveries are more common when this form of analgesia is used and the British Births Survey’ records the injuries to babies that can occur at instrumental deliveries. As far as mothers’ wishes are concerned, we must wait for the results of the survey being done by the Institute for Social Studies in Medical Care before we can be certain of the position. However, the report prepared by the National Childbirth Trust"and the frequency of adverse comment in the Press, on radio and television, and in Parliament certainly suggest that not all parents welcome all recent changes in practice. Though your correspondents are surely right in rejecting closeness to Nature as a reliable measure of obstetric efficacy, they fail to answer Dr Dunn’s most telling point when he asks, where are controlled studies which assess the advantages and hazards of techniques for the active management of labour? Unit for Research
on
Medical
Applications of Psychology, University of Cambridge, 5 Salisbury Villas, Station
Road, Cambridge CB1 2JQ
SIR,-Low serum-triiodothyronine (T3) concentrations have been described in a wide variety of clinical situations. Recent evidence suggests that in fasting obese subjects,12 in patients with hepatic cirrhosis and acute febrile illness,13 and after operation,14 low levels of T3 may result from diversion of thyroxine (1B) monodeiodination towards formation of 3,3 f , 5 f ,-
triiodothyronine (reverse T3, rT3). We have previously demonstrated a progressive decrease in serum-T3 in six patients who died during an acute illness." A similar decrease in the concentration of T4 was observed in five of the six patients. rT3 concentrations have been measured in these same patients, and the results suggest that, after the onset of acute illness, diversion of T4 monodeiodination from T3 to rT3 may also occur. rT3 concentrations increased progressively in all but one of the six patients as T3 concentrations decreased (see figure). In three patients, however, a terminal decrease in rT3 was observed. A similar terminal decrease in rT3 was also observed in four patients who had developed fatal postoperative complications and in whom T3 levels were undeChamberlain, R., Chamberlain, G., Howlett, B., Claireaux, A., British Births 1970; vol. I, the First Week of Life. London, 1975. 6. Butler, N. R., Bonham, D. G. Perinatal Mortality. Edinburgh, 1963. 7. Clayton, S. G., Fraser, D., Lewis, T. L. T. Obstetrics by Ten Teachers. London, 1975. 8. O’Driscoll, K. Br. J. Anœsth 1975, 47, 1053. 9. Scanlon, W. W. Clins Perinat. 1974, 1, 465. 10. Aleksandrowicz, M. K. Merrill-Palmer Q. 1974, 20, 121. 11. Kitzinger, S. Submission to the Department of Health and Social Security 5.
for the National Childbirth Trust. October, 1975. S. W., Chopra, I. J., Sherwin, R. S., Lyall, S S. J. clin. Endocr. Metab. 1976, 42, 197. 13. Chopra, I. J., Chopra, U., Smith, S. R., Reza, M., Solomon, D. H. ibid. 1975, 41, 1043. 14. Burr, W. A., Black, E. G., Griffiths, R. S., Hoffenberg, R., Meinhold, H., Wenzel, K. W. Lancet, 1975, ii, 1277. 15. McLarty, D. G., Raicliffe, W. A., McColl, K., Stone, D., Ratcliffe, J. G. ibid. 1975, ii, 275.
Spaulding,
course
in Tj, 3’ rT and of acute illness.
T.
concentrations in two
patients during
the
In patient A (myocardial infarction) samples were taken from time of admission. In patient B (postoperative complications) measurement of thyroid-hormone concentrations began 1 day after laparotomy-jejunostomy for ischzmic perforation of gastric fundus. Patient A died on day 5 and patient B died on day 7. The horizontal dotted lines indicate the limits of the normal ranges for T3’ rT3, and T,.
MARTIN RICHARDS
THYROID HORMONES IN SERIOUS NON-THYROIDAL ILLNESS
12.
Changes
tectable when thyroid-hormone concentrations were first measured (figure). From these preliminary observations we suggest that the initial response to acute illness involves diversion of T4 monodeiodination from T3 to rT3 formation. If, however, the illness is prolonged and fatal, rT3 concentrations may fall. This decrease in rT3 may be associated with the decline in T, concentration which we have observed. The reason for the decrease in T4 concentration is unknown at present and it cannot be explained solely on the basis of a decrease in the concentration of thyroid-hormone-binding proteins.’s D. G. MCLARTY J. G. RATCLIFFE D. J. SAMMON Stobhill General Hospital, W. A. RATCLIFFE Glasgow G21 3UW Thyroid Research Group, Department of Nuclear Medicine and Endocrinology, Free University, Berlin
K. E. L. MCCOLL H. MEINHOLD K. W. WENZEL
SIR,-Reduced serum concentrations of triiodothyronine (T3) have been reported in various clinical circumstances, including acute and chronic severe illnesses, starvation, and after surgery.1-4 We have made sequential measurements of serum thyroxine (T4), T3, and thyroid-stimulating hormone (T.S.H.) in ten patients with severe, uncontrolled diabetes. Of these patients, eight were in ketoacidosis and two presented a hyperosmolar non-ketotic decompensation. Initial plasma-glucose ranged from 443 to 1344 mg/dl (meants.E.M. 793i93). Arterial blood pH in the eight ketoacidotic cases ranged from 6.75
1.
to
7-22
(mean:ts.E.M. 7.00±0.067). All the patients were
Burger, A., Suter, P., Nicod, P., Vallotton,
M. B., Vagenakis, A., BraverLancet, 1976, i, 653. 2. Carter, J. N., Corcoran, J. M., Eastman, C. J., Lazarus, L. ibid. 1974,ii, man, L.
971.
I. J., Sherwin, R. S., Lyall, S. S. J. clin. Endocr. Metab. 1976, 42, 197. 4. Burr, W. A., Griffiths, R. S., Black, E. G., Hoffenberg, R., Meinhold, H, Wenzel, K. W. Lancet, 1975, ii, 1277. 3.
Spaulding, S. W., Chopra,
1071 SERUM
T4, T3
AND T.S.H. DURING TREATMENT OF DIABETIC COMA IN TEN
PATIENTS
T3 syndrome"
(MEAN±S.E.M.)
is to, be found in metabolic derangements starvation and diabetic ketoacidosis.
common to acute
R. NAEIJE N. CLUMECK G. SOMERS L. VANHAELST J. GOLSTEIN
Faculty of Medicine, University of Brussels, Brussels 1000, Belgium
Statistical analyses we*e e done by paired
t test.
treated with low-dose intravenous insulin.5 The mean duration of treatment was 6h. Blood was drawn every hour until the plasma-glucose reached 200 mg/dl for T3, T4, and T.S.H. determinations. The results are shown in the accompanying table and figure. No statistically significant variation in the serum levels of T4, T.S.H., and T3 could be detected throughout the treatment. The serum-T3 levels were within the hypothyroid range, significantly below those of ten controls (mean+s.E.M. 137±6 ng/dl; P<0.0005 by Student’s t test). Serum T4 and t.s.H. remained in the normal range. One additional patient, a woman aged 67, had a serum-T3 of 140 ng/dl. She was admit-
-
SIR,-We read with interest the article by Dr Burger and his colleagues (March 27, p. 653) on reduced thyroid-hormone levels in acute illness. Several workers have reported that patients with various debilitating illnesses or in acute exacerbations have lower serum-triiodothyronine (T3) concentrations than normal, while the thyroxine (T4) concentration is normal. 1-3 We have studied thyroid-hormone levels in patients with diabetes mellitus and pernicious ansemia. We measured T3 and T.S.H. levels by radioimmunoassay and T4 by competitive protein-binding analysis. In the same sera the antithyroglobulin and thyroid epithelial-cell antimicrosomal antibodies, were also determined. Our results can be seen in the table. In both SERUM
T4
AND
T3
CONCENTRATIONS AND
T/V3 RATIO
diseases the serum-T3 was reduced, while the T4 was normal and theT./T3 ratio was low (r<001). The patients were clinically euthyroid, and the serum-T.S.H. level was normal. We could not find any correlation between the altered thyroid-hormone level and the presence or absence of thyroid antibodies. There was no difference among the various types of diabetes, and the low serum-T3 level was not related to the degree of anaemia. Further studies are necessary to elucidate the cause of this abnormality. We surmise a reduced peripheral conversion of T4 to T3. It is possible that in diabetes mellitus and pernicious ansemia the monodeiodination of T4 is diverted from the conversion of highly potent T to reverse T3, as seen in other systemic illnesses.. Hourly serum-T3
levels
treatment of diabetic
(mean±S.E.M.,
groups of 5-10
patients) during
coma.
1st Department of Medicine, University Medical School, 1083 Budapest, Hungary
EDITH PIROSKA JÁNOS FÖLDES
The boxed area represents the normal values (mean±2s.D. for 10 controls). Point E represents mean serum-T3 at the end of the treatment
for the 10 patients.
EMIGRATION AND INTERNAL LOSS OF PATHOLOGISTS ted with
a
diabetic "ketolactic" acidosis
(arterial blood pH 7-1,
plasma-glucose
940 mg/dl, plasma-p-hydroxybutyrate 6.33 jimoi/ml, plasma-lactate 15-91 mot/ml). After recovery she was found to be hyperthyroid (T. 16.6 flgldl, T3 250 ng/dl, augmented T3-resin uptake). In two of the ketoacidotic patients, we did daily serum-T3 measurements until five days after recovery, while their diabetes was under good control. In the first, serum-T3 was still lowered at the fifth day (60 ng/dl). In the second, serum-T3 returned to normal at the fourth and fifth days (110 and 125 ng/dl).
Thus, diabetic "coma" has to be included in the growing list of clinical states characterised, in the absence of thyroid disease, by lowered serum-T3 levels while T4 and T.S.H. levels remain normal. Nutritional factors, especially dietary carbohydrates, play an important role in the regulation of serum-T33 levels in man.3 Perhaps an explanation for the so-called "low 5.
Clumeck, N., Detroyer, A., Naeije, R., Ectors, M., Balasse, E. O. ibid. 1975, ii, 416.
SIR,-Emigration of doctors has been a matter of concern in Britain for the past two decades, but accurate statistics have been wanting. Numbers for the total yearly exodus have been forthcoming from various sources; but these have not, as a rule, distinguished between true emigrations and temporary absences for limited periods of training or research experience abroad. Furthermore, we know of no breakdown of these total figures into the different categories of doctor. In this uncertain situation the Royal College of Pathologists has thought it desirable to attempt some numerical assessment of the emi’
gration of pathologists. As
a
parallel study
we
have
enquired into
our
internal los-
Carter, J. N., Eastman, C. J., Corcoran, J. M., Lazarus, L. Lancet, 1974, ii, 971. 2. Chopra, I. J., Solomon, D. H., Chopra, U., Young, R. T., Teco, G. N. J. clin. Endocr. Metab. 1974, 39, 501. 3. Järnerot, G., Kågedal, B., von Schenk, H., Truelove, S. C. Acta med. scand. 1976, 199, 229. 4. Chopra, I. J., Chopra, U., Smith, S. R., Rezo, M., Solomon, D. H. J. clin. 1.
Endocr. Metab.
1975, 41, 1043.
Survey 1975’ shows that 68.8% of all mothers received pethidine or levallorphan, a substantial increase from the position in 1958.6 Not only are more mothers receiving this narcotic but dose levels seem to be rising. One textbook,’ for example, suggests that "the usual dose is 150 to 200 mg by intramuscular injection, which may be repeated in 2 hours. A total dose of 300-400 mg is commonly employed though in some hospitals much larger doses are given." Those familiar with the evidence of the physiological and psychological effects 10
of this drug on mothers* and babies9 may well conclude that abuse is very widespread and growing. The evidence for the safety of epidurals is not much more reassuring. Forceps deliveries are more common when this form of analgesia is used and the British Births Survey’ records the injuries to babies that can occur at instrumental deliveries. As far as mothers’ wishes are concerned, we must wait for the results of the survey being done by the Institute for Social Studies in Medical Care before we can be certain of the position. However, the report prepared by the National Childbirth Trust"and the frequency of adverse comment in the Press, on radio and television, and in Parliament certainly suggest that not all parents welcome all recent changes in practice. Though your correspondents are surely right in rejecting closeness to Nature as a reliable measure of obstetric efficacy, they fail to answer Dr Dunn’s most telling point when he asks, where are controlled studies which assess the advantages and hazards of techniques for the active management of labour? Unit for Research
on
Medical
Applications of Psychology, University of Cambridge, 5 Salisbury Villas, Station
Road, Cambridge CB1 2JQ
SIR,-Low serum-triiodothyronine (T3) concentrations have been described in a wide variety of clinical situations. Recent evidence suggests that in fasting obese subjects,12 in patients with hepatic cirrhosis and acute febrile illness,13 and after operation,14 low levels of T3 may result from diversion of thyroxine (1B) monodeiodination towards formation of 3,3 f , 5 f ,-
triiodothyronine (reverse T3, rT3). We have previously demonstrated a progressive decrease in serum-T3 in six patients who died during an acute illness." A similar decrease in the concentration of T4 was observed in five of the six patients. rT3 concentrations have been measured in these same patients, and the results suggest that, after the onset of acute illness, diversion of T4 monodeiodination from T3 to rT3 may also occur. rT3 concentrations increased progressively in all but one of the six patients as T3 concentrations decreased (see figure). In three patients, however, a terminal decrease in rT3 was observed. A similar terminal decrease in rT3 was also observed in four patients who had developed fatal postoperative complications and in whom T3 levels were undeChamberlain, R., Chamberlain, G., Howlett, B., Claireaux, A., British Births 1970; vol. I, the First Week of Life. London, 1975. 6. Butler, N. R., Bonham, D. G. Perinatal Mortality. Edinburgh, 1963. 7. Clayton, S. G., Fraser, D., Lewis, T. L. T. Obstetrics by Ten Teachers. London, 1975. 8. O’Driscoll, K. Br. J. Anœsth 1975, 47, 1053. 9. Scanlon, W. W. Clins Perinat. 1974, 1, 465. 10. Aleksandrowicz, M. K. Merrill-Palmer Q. 1974, 20, 121. 11. Kitzinger, S. Submission to the Department of Health and Social Security 5.
for the National Childbirth Trust. October, 1975. S. W., Chopra, I. J., Sherwin, R. S., Lyall, S S. J. clin. Endocr. Metab. 1976, 42, 197. 13. Chopra, I. J., Chopra, U., Smith, S. R., Reza, M., Solomon, D. H. ibid. 1975, 41, 1043. 14. Burr, W. A., Black, E. G., Griffiths, R. S., Hoffenberg, R., Meinhold, H., Wenzel, K. W. Lancet, 1975, ii, 1277. 15. McLarty, D. G., Raicliffe, W. A., McColl, K., Stone, D., Ratcliffe, J. G. ibid. 1975, ii, 275.
Spaulding,
course
in Tj, 3’ rT and of acute illness.
T.
concentrations in two
patients during
the
In patient A (myocardial infarction) samples were taken from time of admission. In patient B (postoperative complications) measurement of thyroid-hormone concentrations began 1 day after laparotomy-jejunostomy for ischzmic perforation of gastric fundus. Patient A died on day 5 and patient B died on day 7. The horizontal dotted lines indicate the limits of the normal ranges for T3’ rT3, and T,.
MARTIN RICHARDS
THYROID HORMONES IN SERIOUS NON-THYROIDAL ILLNESS
12.
Changes
tectable when thyroid-hormone concentrations were first measured (figure). From these preliminary observations we suggest that the initial response to acute illness involves diversion of T4 monodeiodination from T3 to rT3 formation. If, however, the illness is prolonged and fatal, rT3 concentrations may fall. This decrease in rT3 may be associated with the decline in T, concentration which we have observed. The reason for the decrease in T4 concentration is unknown at present and it cannot be explained solely on the basis of a decrease in the concentration of thyroid-hormone-binding proteins.’s D. G. MCLARTY J. G. RATCLIFFE D. J. SAMMON Stobhill General Hospital, W. A. RATCLIFFE Glasgow G21 3UW Thyroid Research Group, Department of Nuclear Medicine and Endocrinology, Free University, Berlin
K. E. L. MCCOLL H. MEINHOLD K. W. WENZEL
SIR,-Reduced serum concentrations of triiodothyronine (T3) have been reported in various clinical circumstances, including acute and chronic severe illnesses, starvation, and after surgery.1-4 We have made sequential measurements of serum thyroxine (T4), T3, and thyroid-stimulating hormone (T.S.H.) in ten patients with severe, uncontrolled diabetes. Of these patients, eight were in ketoacidosis and two presented a hyperosmolar non-ketotic decompensation. Initial plasma-glucose ranged from 443 to 1344 mg/dl (meants.E.M. 793i93). Arterial blood pH in the eight ketoacidotic cases ranged from 6.75
1.
to
7-22
(mean:ts.E.M. 7.00±0.067). All the patients were
Burger, A., Suter, P., Nicod, P., Vallotton,
M. B., Vagenakis, A., BraverLancet, 1976, i, 653. 2. Carter, J. N., Corcoran, J. M., Eastman, C. J., Lazarus, L. ibid. 1974,ii, man, L.
971.
I. J., Sherwin, R. S., Lyall, S. S. J. clin. Endocr. Metab. 1976, 42, 197. 4. Burr, W. A., Griffiths, R. S., Black, E. G., Hoffenberg, R., Meinhold, H, Wenzel, K. W. Lancet, 1975, ii, 1277. 3.
Spaulding, S. W., Chopra,
1071 SERUM
T4, T3
AND T.S.H. DURING TREATMENT OF DIABETIC COMA IN TEN
PATIENTS
T3 syndrome"
(MEAN±S.E.M.)
is to, be found in metabolic derangements starvation and diabetic ketoacidosis.
common to acute
R. NAEIJE N. CLUMECK G. SOMERS L. VANHAELST J. GOLSTEIN
Faculty of Medicine, University of Brussels, Brussels 1000, Belgium
Statistical analyses we*e e done by paired
t test.
treated with low-dose intravenous insulin.5 The mean duration of treatment was 6h. Blood was drawn every hour until the plasma-glucose reached 200 mg/dl for T3, T4, and T.S.H. determinations. The results are shown in the accompanying table and figure. No statistically significant variation in the serum levels of T4, T.S.H., and T3 could be detected throughout the treatment. The serum-T3 levels were within the hypothyroid range, significantly below those of ten controls (mean+s.E.M. 137±6 ng/dl; P<0.0005 by Student’s t test). Serum T4 and t.s.H. remained in the normal range. One additional patient, a woman aged 67, had a serum-T3 of 140 ng/dl. She was admit-
-
SIR,-We read with interest the article by Dr Burger and his colleagues (March 27, p. 653) on reduced thyroid-hormone levels in acute illness. Several workers have reported that patients with various debilitating illnesses or in acute exacerbations have lower serum-triiodothyronine (T3) concentrations than normal, while the thyroxine (T4) concentration is normal. 1-3 We have studied thyroid-hormone levels in patients with diabetes mellitus and pernicious ansemia. We measured T3 and T.S.H. levels by radioimmunoassay and T4 by competitive protein-binding analysis. In the same sera the antithyroglobulin and thyroid epithelial-cell antimicrosomal antibodies, were also determined. Our results can be seen in the table. In both SERUM
T4
AND
T3
CONCENTRATIONS AND
T/V3 RATIO
diseases the serum-T3 was reduced, while the T4 was normal and theT./T3 ratio was low (r<001). The patients were clinically euthyroid, and the serum-T.S.H. level was normal. We could not find any correlation between the altered thyroid-hormone level and the presence or absence of thyroid antibodies. There was no difference among the various types of diabetes, and the low serum-T3 level was not related to the degree of anaemia. Further studies are necessary to elucidate the cause of this abnormality. We surmise a reduced peripheral conversion of T4 to T3. It is possible that in diabetes mellitus and pernicious ansemia the monodeiodination of T4 is diverted from the conversion of highly potent T to reverse T3, as seen in other systemic illnesses.. Hourly serum-T3
levels
treatment of diabetic
(mean±S.E.M.,
groups of 5-10
patients) during
coma.
1st Department of Medicine, University Medical School, 1083 Budapest, Hungary
EDITH PIROSKA JÁNOS FÖLDES
The boxed area represents the normal values (mean±2s.D. for 10 controls). Point E represents mean serum-T3 at the end of the treatment
for the 10 patients.
EMIGRATION AND INTERNAL LOSS OF PATHOLOGISTS ted with
a
diabetic "ketolactic" acidosis
(arterial blood pH 7-1,
plasma-glucose
940 mg/dl, plasma-p-hydroxybutyrate 6.33 jimoi/ml, plasma-lactate 15-91 mot/ml). After recovery she was found to be hyperthyroid (T. 16.6 flgldl, T3 250 ng/dl, augmented T3-resin uptake). In two of the ketoacidotic patients, we did daily serum-T3 measurements until five days after recovery, while their diabetes was under good control. In the first, serum-T3 was still lowered at the fifth day (60 ng/dl). In the second, serum-T3 returned to normal at the fourth and fifth days (110 and 125 ng/dl).
Thus, diabetic "coma" has to be included in the growing list of clinical states characterised, in the absence of thyroid disease, by lowered serum-T3 levels while T4 and T.S.H. levels remain normal. Nutritional factors, especially dietary carbohydrates, play an important role in the regulation of serum-T33 levels in man.3 Perhaps an explanation for the so-called "low 5.
Clumeck, N., Detroyer, A., Naeije, R., Ectors, M., Balasse, E. O. ibid. 1975, ii, 416.
SIR,-Emigration of doctors has been a matter of concern in Britain for the past two decades, but accurate statistics have been wanting. Numbers for the total yearly exodus have been forthcoming from various sources; but these have not, as a rule, distinguished between true emigrations and temporary absences for limited periods of training or research experience abroad. Furthermore, we know of no breakdown of these total figures into the different categories of doctor. In this uncertain situation the Royal College of Pathologists has thought it desirable to attempt some numerical assessment of the emi’
gration of pathologists. As
a
parallel study
we
have
enquired into
our
internal los-
Carter, J. N., Eastman, C. J., Corcoran, J. M., Lazarus, L. Lancet, 1974, ii, 971. 2. Chopra, I. J., Solomon, D. H., Chopra, U., Young, R. T., Teco, G. N. J. clin. Endocr. Metab. 1974, 39, 501. 3. Järnerot, G., Kågedal, B., von Schenk, H., Truelove, S. C. Acta med. scand. 1976, 199, 229. 4. Chopra, I. J., Chopra, U., Smith, S. R., Rezo, M., Solomon, D. H. J. clin. 1.
Endocr. Metab.
1975, 41, 1043.